The major objective of this research proposal is to study radiation- induced thyroid cancer by coordinated clinical, epidemiological and laboratory investigations. The clinical studies are designed to determine the continuing incidence of radiation-induced thyroid cancer and to evaluate methods of diagnosis and medical and surgical approaches to treatment. This will be accomplished by continuing the longitudinal study of patients who received childhood head and neck irradiation for benign conditions at Michael Reese Hospital. Of the 4,296 patients who were so treated 3,058 (71.2 percent) have been located and 1,025 (33.5 percent) have had surgery for thyroid nodules. Among those who have had surgery, 357 (34.8 percent) have had thyroid cancer. The follow-up of this population will continue with the following aims: (1) to determine the continuing incidence of radiation-induced thyroid cancer, (2) to determine if their radiation-induced thyroid cancers have the same age- dependent worsening prognosis as seen in the general population, and (3) to evaluate the diagnostic methods and treatment methods that have been used. Laboratory studies will focus on the role of serum thyroglobulin in the diagnosis of thyroid tumors. Parallel studies will continue on other radiation-induced tumors, including benign and malignant salivary tumors, neural tumors, parathyroid tumors and others. Together these will provide the information to develop guidelines for the care of persons with a history of radiation. Epidemiological studies will focus on identifying evidence for the existence of heritable radiation susceptibility factors. Patterns of multiple tumors in irradiated individuals and family histories of cancer will be analyzed. Specimens of neoplasms from previous surgery will be used to study specific oncogenes as markers of and as participants in radiation-induced neoplastic transformation. These studies will focus on rearrangements of the ret protooncogene in thyroid neoplasms and the NF2 tumor suppressor gene in neural tumors.